Explosive drug information in the time of COVID-19

In times of crises, findings are published quickly, spreading around the world within minutes. The validity and accuracy of new information is more important than ever, even though the general demand for rapid knowledge gain may mislead scientists into publishing results without close scrutiny. Missing robust evidence could be responsible for fake or even ugly news, unsettling the general population worldwide. In this sense, we would like to share an example, supporting the recent editorial by Watson and Tsuyuki in this journal. ¹

During the COVID-19 pandemic, there have been countless recommendations in public and social media to stop the intake of the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen because of an increased risk for SARS-CoV-2 infection and severity of COVID-19 disease; this included eventual retractions. ² Fang et al. ³ was cited, and the recommendation to avoid ibuprofen most probably refers to the following statement in their correspondence, which, overall, addressed the issue of hypertension, use of angiotensin-converting enzyme (ACE) inhibitors and the risk of COVID-19: “ACE2 can also be increased by thiazolidinediones and ibuprofen. These data suggest that ACE2 expression is increased in diabetes . . . . Consequently, the increased expression of ACE2 would facilitate infection with COVID-19. We therefore hypothesise that . . . treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19.” ² To the best of our knowledge, both experimental and clinical data are still missing to confirm these statements.

After further research concerning ibuprofen and ACE2, we found a paper published by Qiao et al. in 2015. ⁴ In this work, the effect of ibuprofen on cardiac fibrosis was investigated in streptozotocin-induced diabetic rats. As a result, ACE2 levels were reduced in diabetic as compared with control rats. After the administration of ibuprofen (or the thiazolidinedione pioglitazone), the authors observed an upregulation of ACE2 in the diabetic rats. However, ACE2 levels were lower in comparison with healthy rats. The original correspondence of Fang et al. ³ was later corrected ⁵ but not with regard to the ibuprofen statement. Thus, in addition to the absence of any clinical data, there was (and still is) no experimental evidence indicating that ibuprofen should be avoided in SARS-CoV-2–infected patients.

In accordance, the European Medicines Agency (EMA) gave immediate advice on the use of ibuprofen for COVID-19 and recommends patients and health care professionals to “consider all available treatment options including paracetamol and NSAIDs.” ⁶ Applicable for the treatment of fever or pain in COVID-19 infection, ibuprofen (or paracetamol) should be used “at the lowest effective dose and for the shortest possible period.”

Until there is robust evidence, unconfirmed scientific statements should not fuel the suspicion about the probable impact of ibuprofen (or any other xenobiotic) on the course of COVID-19, which has led to shortages of paracetamol (acetaminophen) drug products. In accordance with the Federal Ministry of Health, the Drug Commission of German Pharmacists in March 2020 asked pharmacists to dispense and physicians to prescribe paracetamol only if needed and to limit the number of tablets to treat the actual course of a disease. ⁷ More than ever, sharing (new) information referring to COVID-19 must be carried out responsibly, and pharmacists are key in combating mis/disinformation.

—Martin Schulz, RPh, PhD, FFIP, FESCP

—Pia M. Schumacher, RPh, PhD

—Juliana Schneider, RPh

—André Said, RPh, PhD
Drug Commission of German Pharmacists (AMK)
Berlin, Germany

—Ulrich Laufs, MD
Department of Cardiology, University Hospital Leipzig
Leipzig, Germany